Neuropilin-1 and placental growth factor as prognostic factors in metastatic breast cancer.

BACKGROUND: Angiogenesis is crucial for tumor development, progression, and metastasizing. The most important regulator of angiogenesis is the vascular endothelial growth factor (VEGF) family, which is involved in multiple pathways in tumor microenvironment. The objective of this study was to investigate the prognostic value of the VEGF family in patients treated for metastatic breast cancer. The emphasis was on neuropilin-1 (NRP-1) and placental growth factor (PlGF). MATERIALS AND METHODS: An analysis of eight members of the VEGF family was performed using baseline plasma samples of 65 patients treated for metastatic HER2 negative breast cancer in a phase II first-line bevacizumab plus chemotherapy trial. The patients were divided into two groups, high or low, according to the median for each VEGF family member. Progression-free survival (PFS) and overall survival (OS) were determined for each VEGF family member. RESULTS: The patients with low plasma levels of NRP-1 and PlGF had a longer OS than those with high plasma levels [multivariable adjusted hazard ratios (HRs) 2.54 (95% confidence interval (CI) 1.11-5.82, p = 0.02) and 3.11 (95% CI 1.30-7.47, p = 0.01), respectively]. The patients with low levels of both NRP-1 and PlGF had a remarkably long OS with HR of 6.24, (95% CI 1.97-19.76, p = 0.002). In addition, high baseline NRP-1 level was associated with a significantly shorter PFS [multivariable adjusted HR 2.90 (95% CI 1.02-8.28, p = 0.04)] than that in the low-level group, and a high baseline vascular endothelial growth factor receptor-2 level was associated with a longer PFS [multivariable adjusted HR 0.43 (95% CI 0.19-0.98, p = 0.04)]. CONCLUSION: Especially NRP-1 and PlGF have prognostic potential in metastatic breast cancer patients treated with a bevacizumab-taxane combination. Patients with low plasma levels of NRP-1 or PlGF have longer OS than patients with high levels. Patients with both low NRP-1 and PlGF levels appear to have excellent long-term survival. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00979641, registration date 18/09/2009. The regional Ethics Committee: R08142M, registration date 18/11/2008.

Breast density and the likelihood of malignant MRI-detected lesions in women diagnosed with breast cancer.

OBJECTIVES: To assess whether mammographic breast density in women diagnosed with breast cancer correlates with the total number of incidental magnetic resonance imaging (MRI)-detected lesions and the likelihood of the lesions being malignant. METHODS: Patients diagnosed with breast cancer meeting the EUSOBI and EUSOMA criteria for preoperative breast MRI routinely undergo mammography and ultrasound before MRI at our institution. Incidental suspicious breast lesions detected in MRI are biopsied. We included patients diagnosed with invasive breast cancers between 2014 and 2019 who underwent preoperative breast MRI. One reader retrospectively determined breast density categories according to the 5th edition of the BI-RADS lexicon. RESULTS: Of 946 patients with 973 malignant primary breast tumors, 166 (17.5%) had a total of 175 (18.0%) incidental MRI-detected lesions (82 (46.9%) malignant and 93 (53.1%) benign). High breast density according to BI-RADS was associated with higher incidence of all incidental enhancing lesions in preoperative breast MRIs: 2.66 (95% confidence interval: 1.03-6.86) higher for BI-RADS density category B, 2.68 (1.04-6.92) for category C, and 3.67 (1.36-9.93) for category D compared to category A (p < 0.05). However, high breast density did not predict higher incidence of malignant incidental lesions (p = 0.741). Incidental MRI-detected lesions in the contralateral breast were more likely benign (p < 0.001): 18 (27.3%)/48 (72.7%) vs. 64 (58.7%)/45 (41.3%) malignant/benign incidental lesions in contralateral vs. ipsilateral breasts. CONCLUSION: Women diagnosed with breast cancer who have dense breasts have more incidental MRI-detected lesions, but higher breast density does not translate to increased likelihood of malignant incidental lesions. CLINICAL RELEVANCE STATEMENT: Dense breasts should not be considered as an indication for preoperative breast MRI in women diagnosed with breast cancer. KEY POINTS: • The role of preoperative MRI of patients with dense breasts diagnosed with breast cancer is under debate. • Women with denser breasts have a higher incidence of all MRI-detected incidental breast lesions, but the incidence of malignant MRI-detected incidental lesions is not higher than in women with fatty breasts. • High breast density alone should not indicate preoperative breast MRI.

Radiological and pathological assessment of response to neoadjuvant CDK4/6 inhibitor and endocrine treatments in a real-life setting-initial results.

BACKGROUND: Neoadjuvant endocrine therapy is an alternative to neoadjuvant chemotherapy in women with inoperable luminal-like breast cancers. Neoadjuvant cyclin-dependent kinase 4/6 inhibitor treatment combined with endocrine treatment (CDK4/6I + E) is interesting given the combination's utility in the treatment of metastatic breast cancer. Currently, the literature on the radiological response evaluation of patients treated with neoadjuvant CDK4/6I + E in a real-life setting is scarce. PURPOSE: To conduct a radiological response evaluation of patients treated with neoadjuvant CDK4/6I + E in a real-life setting. MATERIAL AND METHODS: We retrospectively reviewed clinical, pathological, and radiological findings of six patients with luminal-like breast cancers treated with neoadjuvant CDK4/6I + E treatment. The radiological neoadjuvant CDK4/6I + E response was evaluated with the RECIST 1.1 criteria and the pathological residual disease was assessed using the Residual Cancer Burden (RBC) criteria. RESULTS: None of the patients achieved a complete radiological magnetic resonance imaging (MRI)-determined response or a complete pathological response; three (50%) patients had a partial radiological response; in the three others, the disease remained stable radiologically. All of the tumors were rendered susceptible to surgical treatment. Two out of six (33.3%) patients had a moderate response (RBC-II); four (66.7%) had an extensive residual disease (RBC-III) in the final surgical sample. CONCLUSION: Although none of the patients achieved a pathologically complete response, neoadjuvant CDK4/6I + E treatment rendered all tumors operable. MRI appears to be reliable in the assessment of the neoadjuvant CDK4/6I + E treatment response in a real-life setting. Larger studies are warranted to confirm these results.

Plasma levels of soluble urokinase-type plasminogen activator receptor associate with the clinical severity of acute Puumala hantavirus infection.

OBJECTIVES: Urokinase-type plasminogen activator receptor is a multifunctional glycoprotein, the expression of which is increased during inflammation. It is known to bind to ß3-integrins, which are elementary for the cellular entry of hantaviruses. Plasma soluble form of the receptor (suPAR) levels were evaluated as a predictor of severe Puumala hantavirus (PUUV) infection and as a possible factor involved in the pathogenesis of the disease. DESIGN: A single-centre prospective cohort study. SUBJECTS AND METHODS: Plasma suPAR levels were measured twice during the acute phase and once during the convalescence in 97 patients with serologically confirmed acute PUUV infection using a commercial enzyme-linked immunosorbent assay (ELISA). RESULTS: The plasma suPAR levels were significantly higher during the acute phase compared to the control values after the hospitalization (median 8.7 ng/ml, range 4.0-18.2 ng/ml vs. median 4.7 ng/ml, range 2.4-12.2 ng/ml, P<0.001). The maximum suPAR levels correlated with several variables reflecting the severity of the disease. There was a positive correlation with maximum leukocyte count (r = 0.475, p<0.001), maximum plasma creatinine concentration (r = 0.378, p<0.001), change in weight during the hospitalization (r = 0.406, p<0.001) and the length of hospitalization (r = 0.325, p = 0.001), and an inverse correlation with minimum platelet count (r = -0.325, p = 0.001) and minimum hematocrit (r = -0.369, p<0.001). CONCLUSION: Plasma suPAR values are markedly increased during acute PUUV infection and associate with the severity of the disease. The overexpression of suPAR possibly activates ß3-integrin in PUUV infection, and thus might be involved in the pathogenesis of the disease.